Immuno-Modulatory Effects of Microparticles Formulated from Degradable Polystyrene Analogue.

Environmental accumulation of non-degradable polystyrene (PS) microparticles from plastic waste poses potential adverse impact on marine life and human health. Herein, microparticles from a degradable PS analogue (dePS) are formulated and their immuno-modulatory characteristics are comprehensively evaluated. Both dePS copolymer and microparticles are chemically degradable under accelerated hydrolytic condition. In vitro studies show that dePS microparticles are non-toxic to three immortalized cell lines. While dePS microparticles do not induce macrophage polarization in vitro, dePS microparticles induce in vivo upregulation of both pro-inflammatory and anti-inflammatory biomarkers in immuno-competent mice, suggesting the coexistence of mixed phenotypes of macrophages in the host immune response to these microparticles. Interestingly, on day 7 following subcutaneous in mice, dePS microparticles induce a lower level of several immuno-modulatory biomarkers (matrix metallo-proteinases (MMPs), tumor necrosis factor (TNF-α), and arginase activity) compared to that of reference poly(lactic-co-glycolic acid) microparticles. Remarkably, compared to PS microparticles, dePS microparticles exhibit similar in vitro and in vivo bioactivity while acquiring additional chemical degradability. Overall, this study gains new insights into the host immune response to dePS microparticles and suggests that this dePS analogue might be explored as an alternative material choice for biomedical and consumer care applications.

Modular design of a hybrid hydrogel for protease-triggered enhancement of drug delivery to regulate TNF-α production by pro-inflammatory macrophages.

Systemic drug administration has conventionally been prescribed to alleviate persistent local inflammation which is prevalent in chronic diseases. However, this approach is associated with drug-induced toxicity, particularly when the dosage exceeds that necessitated by pathological conditions of diseased tissues. Herein, we developed a modular hybrid hydrogel which could be triggered to release an anti-inflammatory drug upon exposure to elevated protease activity associated with inflammatory diseases. Modular design of the hybrid hydrogel enabled independent optimization of its protease-cleavable and drug-loaded subdomains to facilitate hydrogel formation, cleavability by matrix-metalloprotease-9 (MMP-9), and tuning drug release rate. In vitro study demonstrated the protease-triggered enhancement of drug release from the hybrid hydrogel system for effective inhibition of TNF-α production by pro-inflammatory macrophages and suggested its potential to mitigate drug-induced cytotoxicity. Using non-invasive imaging to monitor the activity of reactive oxygen species in biomaterial-induced host response, we confirmed that the hybrid hydrogel and its constituent materials did not induce adverse immune response after 5 days following their subcutaneous injection in immuno-competent mice. We subsequently incorporated this hybrid hydrogel onto a commercial wound dressing which could release the drug upon exposure to MMP-9. Together, our findings suggested that this hybrid hydrogel might be a versatile platform for on-demand drug delivery via either injectable or topical application to modulate inflammation in chronic diseases.

An Unprecedented Knot-like G-Quadruplex Peripheral Motif.

A knot-like G-quadruplex peripheral structure is formed by a 7-nt DNA sequence DL7 (TGTTGGT), in which six out of its seven nucleobases participate in compact base-pairing interactions. Here, the solution NMR structure of a 24-nt DNA oligonucleotide containing the DL7 sequence shows the interaction between a two-layer anti-parallel G-quadruplex core and the peripheral knot-like structure, including the construction of two sharp turns in the DNA backbone. The formation of this novel structural element highlights the intricate properties of single-stranded DNA folding in presence of G-quadruplex-forming motifs. We demonstrated the compatibility of the DL7 knot-like structure with various G-quadruplexes, which could have implications in drug design and DNA engineering.

G-quadruplex structure of an anti-proliferative DNA sequence.

AGRO100 (also known as AS1411) is a G-rich oligonucleotide that has long been established as a potent anti-cancer aptamer. However, the structure of AGRO100 remained unresolved, due to the co-existence of multiple different G-quadruplex conformations. We identified a DNA sequence named AT11, derived from AGRO100, which formed a single major G-quadruplex conformation and exhibited a similar anti-proliferative activity as AGRO100. The solution structure of AT11 revealed a four-layer G-quadruplex comprising of two propeller-type parallel-stranded subunits connected through a central linker. The stacking between the two subunits occurs at the 3΄-end of the first block and the 5΄-end of the second block. The structure of the anti-proliferative DNA sequence AT11 will allow greater understanding on the G-quadruplex folding principles and aid in structural optimization of anti-proliferative oligonucleotides.

Platinum and palladium nanotubes based on genetically engineered elastin-mimetic fusion protein-fiber templates: synthesis and application in lithium-O2 batteries.

The coupling of proteins with self-assembly properties and proteins that are capable of recognizing and mineralizing specific inorganic species is a promising strategy for the synthesis of nanoscale materials with controllable morphology and functionality. Herein, GPG-AG3 protein fibers with both of these properties were constructed and served as templates for the synthesis of Pt and Pd nanotubes. The protein fibers of assembled GPG-AG3 were more than 10 µm long and had diameters of 20-50 nm. The as-synthesized Pt and Pd nanotubes were composed of dense layers of ~3-5 nm Pt and Pd nanoparticles. When tested as cathodes in lithium-O2 batteries, the porous Pt nanotubes showed low charge potentials of 3.8 V, with round-trip efficiencies of about 65% at a current density of 100 mA g(-1).